DESCRIPTION (Taken from the application): Osteoarthritis (OA) is a major disease affecting the US population that has been reported to be almost universal in people 65 years of age or older. Health), human synovial joints are remarkable bearings which exhibit extremely low coefficients of friction and can withstand high cyclic stresses. Cartilage homeostasis is maintained by articular chondrocytes. The present situation regarding the prevention and control of primary OA is unsatisfactory due to a lack of knowledge of the etiology and pathogenesis of the disease. A better understanding of the role of cytokines in chondroprotection is needed. Our hypothesis is that mechanical stimulation maintains cartilage homeostasis via a synergistic regulation of growth factors. Our long-term goal is to determine how mechanical stimulation influences growth factor-mediated response of chondrocytes and to utilize this coupling for the development of replacement cartilage. This R03 proposal is an initial step in our experimental plan. We will pursue three specific aims - (1) Quantify the effect of IGF-I and IL-1beta on cellular response (Proliferation, Collagen Type II/Proteoglycan Metabolism) in non-loaded alginate-chondrocyte hydrogels; (2) Construct, validate, and utilize our mechanical device for in vitro compression of cellular hydrogel systems in static and dynamic regimes; and (3) Determine the effect of mechanical stimulation coupled with cytokine regulatory molecules (IGF-I, IL-1beta). Our model system consists of equine articular chondrocytes in alginate hydrogels. At the completion of this project we will have the components in place to apply for an RO1 grant from NIH. This support is critical for the initiation of our long-term studies regarding mechanical-hormonal synergism in regulating normal cartilage and, by extension, what is lacking in OA cartilage.